title: Negative depletion of α/β+ T cells and of CD19+ B lymphocytes: a novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation.
abstract: In recent years, infusion of T-cell depleted hematopoietic stem cells from an HLA-haploidentical relative has been shown to represent a suitable and effective, alternative option in patients in need of an allograft who lack an HLA-identical relative. In particular, this type of allograft is associated with the enormous advantage of offering an immediate transplant treatment to virtually all pediatric patients without an HLA-matched donor, whether related or unrelated, or a suitable umbilical cord blood unit. Several studies have shown that in patients given a T-cell depleted transplant relevant part of the anti-leukemia effect is mediated by alloreactive (i.e. KIR/HLA mismatched) Natural Killer cells originated from donor hematopoietic stem cells. After infusion of positively selected hematopoietic stem cell, fully functioning Natural Killer cells emerge in the recipient peripheral blood, persisting over time, only several weeks after the allograft. We have developed a new method of T-cell depletion (based on the physical elimination of mature T cells carrying α and β chains of the T-cell receptor), which permits to maintain mature donor-derived alloreactive Natural Killer cells and γδ(+) T cells in the graft. We, thus, started a formal study in children with hematological disorders aimed at evaluating the safety and efficacy of this approach. Preliminary results on 60 children transplanted so far after this type of graft manipulation are particularly promising.
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Ospedale Bambino Gesù, Rome, Italy; University of Pavia, Italy. Electronic address: franco.locatelli@opbg.net.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Aurelie
authors.initials: A
authors.lastname: Bauquet
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretta
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D006680:HLA Antigens / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: ALL; AML; Allogeneic hematopoietic stem cell transplantation; GvHD; GvL; HSC; HSCT; MDS; NK; NK cell maturation; Selective T-cell depletion; T cell receptor; TCR; UCB; acute lymphoblastic leukemia; acute myeloid leukemia; graft-versus-host disease; graft-versus-leukemia; hematopoietic stem cell; hematopoietic stem cell transplantation; myelodysplastic syndromes; natural killer; umbilical cord blood; γδ(+) T cells